4-[[4-(aminocarbonyl)phenyl]azo]-N-(2-ethoxyphenyl)-3-hydroxynaphthalene-2-carboxamide

Endpoint summary

Description of key information

Single oral application of 15000 mg test substance per kg bw did not cause lethality in female Wistar-rats during the 14 day observation period, resulting in a LD50 > 15000 mg/kg bw.

Single dermal application of the test item to rats at a dose of 2000 mg/kg body weight was associated with neither mortality nor signs of toxicity. The dermal LD50 was determined to be > 2000 mg / kg body weight.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From 07 APR 1976 to 21 APR 1976

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Basic data given: comparable to guidelines

Qualifier:

according to guideline

Guideline:

other: company guideline similar to OECD guideline 401

Deviations:

no

GLP compliance:

no

Remarks:

GLP was not compulsory at the time the study was conducted

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Hoechst AG, breeding colony
- Weight at study initiation: 90 to 110 g
- Fasting period before study: 16 h
- Housing: plastic cages
- Diet: Altromin 1324 (Altromin GmbH, Lage/Lippe, Germany), ad libitum
- Water: tap water, ad libitum

Route of administration:

oral: gavage

Vehicle:

other: sesame oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 25 %

Doses:

15000 mg/kg bw

No. of animals per sex per dose:

10

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of weighing: weekly
- Necropsy of survivors performed: yes

Sex:

female

Dose descriptor:

LD50

Effect level:

> 15 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: no animals died within the observation period

Mortality:

- no death occurred.

Clinical signs:

other: - no animal showed any clinical symptoms - faeces was red-coloured

Gross pathology:

- animals killed at the end of the observation period showed no macroscopically visible changes

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Single application of 15000 mg test substance per kg bw did not cause lethality in female Wistar-rats during the 14 day observation period, resulting in a LD50 > 15000 mg/kg bw.

Executive summary:

Female Wistar-rats were subjected to test acute oral toxicity. The test substance was administered by gavage at a dose of 15000 mg/kg bw (25 % suspension in sesame oil). No animal died during the 14 day observation period, resulting in a LD50 >15000 mg/kg bw.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD0

Value:

>= 15 000 mg/kg bw

Quality of whole database:

reliable

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

From 12 MAY 1981 to 26 MAY 1981

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

other: Does not meet important criteria of today standard methods (diameter of particulates not determined, insufficient reporting of exposure concentration, no data on test item purity)

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Qualifier:

according to guideline

Guideline:

other: company guideline similar to OECD guideline 403

Deviations:

no

GLP compliance:

no

Remarks:

GLP was not compulsory at the time the study was conducted

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

male/female

Route of administration:

inhalation: dust

Type of inhalation exposure:

nose only

Vehicle:

air

Analytical verification of test atmosphere concentrations:

yes

Remarks:

gravimetric

Duration of exposure:

4 h

Remarks on duration:

14 days observation period

Concentrations:

mean 1580 mg/cubic metre (787-2479)

No. of animals per sex per dose:

6

Control animals:

not specified

Details on study design:

- test concentration was the highest technically feasible concentration

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 1 580 mg/m³ air

Based on:

test mat.

Exp. duration:

4 h

Remarks on result:

other: no animal died during exposure or post observation period (highest technically feasible concentration)

- animals showed irregular breathing during exposure

- no animal died during exposure or post observation period

- normal body weight development during post observation period

- no macroscopic findings at necropsy

Conclusions:

The test item was not toxic when administerd to rats via nose-only inhalation at the highest technically feasible concentration of 1580 mg per cubic metre.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LC0

Value:

>= 1.58 mg/L air

Physical form:

inhalation: dust

Quality of whole database:

supporting data, reliability unknown

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From 02 MAR 2012 to 08 MAY 2012

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline study (OECD 402), GLP-compliant

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1200 (Acute Dermal Toxicity)

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

- Full barrier in an air-conditioned room
- Temperature: 22 +/- 3 °C
- Relative humidity: 55 +/- 10%
- Artificial light, sequence being 12 hours light, 12 hours dark
- Air change: 10 x / hour
- Free access to Altromin 1324 maintenance diet for rats and mice (lot no. 1114)
- Free access to tap water, sulphur acidified to a pH value of approximately 2.8
(drinking water, municipal residue control, microbiological controls at regular intervals)
- The animals were kept individually in IVC cages, type III H, polysulphone cages on Altromin
saw fibre bedding (lot no. 110811)
- Certificates of food, water and bedding are filed at BSL BIOSERVICE
- Adequate acclimatisation period (at least five days) under laboratory conditions

Type of coverage:

semiocclusive

Vehicle:

cotton seed oil

Details on dermal exposure:

Preparation of the Animals:
The animals were marked for individual identification by tail painting.
Approximately 24 hours before the test, the fur was removed from the dorsal area of the trunk using an electric clipper.
Care was taken to avoid abrading the skin, and only animals with healthy intact skin were used.
No less than 10% of the body surface was cleared for the application.
Prior to the application a detailed clinical observation was made of all animals.

Application:
The test item was applied at a single dose, uniformly over an area which was approximately 10% of the total body surface. In order to ensure good skin contact the test item was moistened with the vehicle.
The test item was held in contact with the skin by a dressing throughout a 24-hour period.
The dressing consisted of a gauze-dressing and non-irritating tape and was fixed with an additional dressing in a suitable manner.

Duration of exposure:

The test item was held in contact with the skin throughout a 24-hour period. At the end of the exposure period the residual test item was removed using cottonseed oil.

Doses:

The test item was applied at a single dose of 2000 mg/kg body weight to each animal.

No. of animals per sex per dose:

5 male and 5 female

Control animals:

not required

Details on study design:

Observation period:
All animals were observed for 14 days after dosing

Weight Assessment:
The animals were weighed on day 1 (prior to the application) and on days 8 and 15.

Clinical Examination:
careful clinical examination was made several times on the day of dosing (at least once during the first 30 minutes
and with special attention given during the first 4 hours post-dose). As soon as symptoms were noticed they were recorded.
Thereafter, the animals were observed for clinical signs once daily until the end of the observation period. All abnormalities
were recorded. Cageside observations included changes in the skin and fur, eyes and mucous membranes.
Also respiratory, circulatory, autonomic and central nervous systems and somatomotor activity and behaviour
pattern were examined. Attention was directed to observations of tremors, convulsions, salivation, diarrhoea,
lethargy, sleep and coma.

Pathology:
At the end of the observation period the surviving animals were sacrificed with an overdosage of pentobarbital injected
intraperitoneally (Narcoren®, Merial) at the dosage of approximately 8 mL/kg bw. All animals were subjected to gross necropsy.
All gross pathological changes were recorded and in case of findings the tissues were preserved for a possible
histopathological evaluation. The preserved tissues of which no histopathological evaluation was made will be discarded
3 months after the release of the final report unless otherwise agreed upon with the sponsor.

Evaluation of Results:
Individual reactions of each animal were recorded at each time of observation.
Toxic response data were recorded by sex and dose level.
Nature, severity and duration of clinical observations were described.
The body weight changes were summarised in a tabular form.
Necropsy findings were described.

Statistics:

According to OECD guidelines, the biological relevance of the results is the criterion for the interpretation of results, a statistical evaluation of the results is not regarded as necessary.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

other: Content C.I.

Remarks on result:

other: no animal died within 14 d observation period

Mortality:

No mortality was observed

Clinical signs:

other: No treatment-related effects were observed

Gross pathology:

No treatment-related effects were observed

Other findings:

No erythema or oedema was observed. Scratches were observed in 1 of 5 male animals.

Table Absolute Body Weights in g and Body Weight Gain in %:

Dose: 2000 mg/kg body weight
Animal No. / Sex	g Day 1	g Day 8	g Day 15	% Day 1-15
21 / male	227	242	276	22
22 / male	236	251	277	17
23 / male	229	248	278	21
24 / male	230	241	274	19
25 / male	245	260	280	14
26 / female	216	220	223	3
27 / female	213	214	221	4
28 / female	218	215	217	-0.50
29 / female	215	218	223	4
30 / female	207	211	220	6

Table LD50:

Dose (Unit)	Number of Animals Investigated	Number of Intercurrent Deaths	LD50
2000 mg/kg bw	5 males	0	> 2000 mg/kg bw
2000mg/kg bw	5 females	0	> 2000 mg/kg bw

bw = body weight

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Under the conditions of the present study, single dermal application of the test item to rats at a dose of 2000 mg/kg body weight was associated with neither mortality nor signs of toxicity. In one male animal scratches were observed from day 6 until the end of the observation period which might be caused by scratching activities of the animal. The dermal LD50 was determined to be > 2000 mg / kg body weight.

Executive summary:

Acute toxicity after dermal application was investigated in Wistar rats according to an OECD 402 limit test. Animals (5 males and 5 females) were applied 2000 mg/kg bw in cottonseed oil for 24 hours. No animal died during the observation period.

Table1:  Results per Step

Sex	Dose (mg/kg bw)	Number of Animals	Number of Intercurrent Deaths
male	2000	5	0
female	2000	5	0

Signs of toxicity related to dose level used, time of onset and duration:

No treatment-related effects were observed

Effect on organs (related to dose level):

No treatment-related effects were observed.

Signs of irritation:

No erythema or oedema was observed. Scratches were observed in 1 of 5 male animals.

Conclusion

Under the conditions of the present study, single dermal application of the test item to rats at a dose of 2000 mg/kg body weight was associated with neither mortality nor signs of toxicity. In one male animal scratches were observed from day 6 until the end of the observation period which might be caused by scratching activities of the animal.

The dermal LD50 was determined to be > 2000 mg / kg body weight.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD0

Value:

>= 2 000 mg/kg bw

Quality of whole database:

reliable without restriction

Justification for classification or non-classification

No classification

The test material did not cause acute toxic effects after acute oral, dermal or inhalation exposure of rats at maximal doses.